One Stone Two Birds-Enantioselective Bimetallic Catalysis for α-Amino Acid Derivatives with an Allene Unit

Main observation and conclusion A highly enantioselective 2,3-allenylation of acyclic and cyclic alpha-imino carboxylates via a synergistic bimetallic Pd/Cu catalysis with the same commercially available (R,R-p)-Pr-i-FOXAP (also as Phosferrox, (R,R)-[2-(4'-i-propyloxazolin-2'-yl)ferrocenyl]diphenyl phosphine) ligand for both metals affording optically active 2,3-butadienyl alpha-amino acid derivatives in high to excellent yields with excellent enantioselectivities has been developed. The synthetic versatility of this reaction has been demonstrated by gram-scale synthesis, a catalytic enantioselective synthesis of naturally occurring (S)-2-amino-4,5-hexadienoic acid A, and conversions to several useful chemicals, such as optically active alpha-amino acids, beta-amino alcohols, potential chiral oxazoline ligands bearing an allenic moiety, and bicyclic ketone compounds. A mechanism involving the roles of two metals and the single chiral ligand has been extensively studied based on the isolation of key palladium pre-catalyst and control experiments.

Automated summary

A highly enantioselective 2,3-allenylation of acyclic and cyclic alpha-imino carboxylates has been developed using a synergistic bimetallic Pd/Cu catalysis with a commercially available ligand, resulting in optically active derivatives with excellent enantioselectivities. The reaction's synthetic versatility has been demonstrated through gram-scale synthesis, as well as the conversion to various useful compounds.